Biomarkers associated with clinical manifestations in Fabry disease patients with a late-onset cardiac variant mutation.

BACKGROUND: Fabry disease is a lysosomal storage disorder with an incidence of 1:1600 for the late-onset IVS4+919G>A cardiac variant mutation in Taiwan. Signs and symptoms of this cardiac variant include left ventricular hypertrophy, mitral insufficiency and/or arrhythmias. The search for biomarkers that might predict the clinical outcomes and guide treatment options is important. We thus investigated relationships between Fabry disease biomarkers (such as globotriaosylceramide (Gb3), globotriaosylsphingosine (lyso-Gb3)/related analogues) and age, gender, enzyme activity, clinical manifestations and severity of the disease in these patients.

METHOD: Urine and plasma biomarkers were analyzed using tandem mass spectrometry. A large cohort of 191 adult and pediatric Fabry patients carrying the IVS4+919G>A mutation was studied. Some patients were members of the same family.

RESULTS: Our results show that the plasma lyso-Gb3 level, and urinary analogue levels of lyso-Gb3 at m/z (+16), (+34), and (+50) adjusted for gender and age had a positive association with the left ventricular mass index, and/or the Mainz Severity Score Index.

CONCLUSIONS: It might thus be of particular interest to monitor children with high levels of these biomarkers, as part of a longitudinal study in order to determine if the excretion profile at a young age is predictive of the outcomes of disease severity in adulthood.